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An Interspecies Regulatory Network Inferred from Simultaneous RNA-seq of Candida albicans Invading Innate Immune Cells
The ability to adapt to diverse micro-environmental challenges encountered within a host is of pivotal importance to the opportunistic fungal pathogen Candida albicans. We have quantified C. albicans and M. musculus gene expression dynamics during phagocytosis by dendritic cells in a genome-wide, ti...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Research Foundation
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299011/ https://www.ncbi.nlm.nih.gov/pubmed/22416242 http://dx.doi.org/10.3389/fmicb.2012.00085 |
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author | Tierney, Lanay Linde, Jörg Müller, Sebastian Brunke, Sascha Molina, Juan Camilo Hube, Bernhard Schöck, Ulrike Guthke, Reinhard Kuchler, Karl |
author_facet | Tierney, Lanay Linde, Jörg Müller, Sebastian Brunke, Sascha Molina, Juan Camilo Hube, Bernhard Schöck, Ulrike Guthke, Reinhard Kuchler, Karl |
author_sort | Tierney, Lanay |
collection | PubMed |
description | The ability to adapt to diverse micro-environmental challenges encountered within a host is of pivotal importance to the opportunistic fungal pathogen Candida albicans. We have quantified C. albicans and M. musculus gene expression dynamics during phagocytosis by dendritic cells in a genome-wide, time-resolved analysis using simultaneous RNA-seq. A robust network inference map was generated from this dataset using NetGenerator, predicting novel interactions between the host and the pathogen. We experimentally verified predicted interdependent sub-networks comprising Hap3 in C. albicans, and Ptx3 and Mta2 in M. musculus. Remarkably, binding of recombinant Ptx3 to the C. albicans cell wall was found to regulate the expression of fungal Hap3 target genes as predicted by the network inference model. Pre-incubation of C. albicans with recombinant Ptx3 significantly altered the expression of Mta2 target cytokines such as IL-2 and IL-4 in a Hap3-dependent manner, further suggesting a role for Mta2 in host–pathogen interplay as predicted in the network inference model. We propose an integrated model for the functionality of these sub-networks during fungal invasion of immune cells, according to which binding of Ptx3 to the C. albicans cell wall induces remodeling via fungal Hap3 target genes, thereby altering the immune response to the pathogen. We show the applicability of network inference to predict interactions between host–pathogen pairs, demonstrating the usefulness of this systems biology approach to decipher mechanisms of microbial pathogenesis. |
format | Online Article Text |
id | pubmed-3299011 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Frontiers Research Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-32990112012-03-13 An Interspecies Regulatory Network Inferred from Simultaneous RNA-seq of Candida albicans Invading Innate Immune Cells Tierney, Lanay Linde, Jörg Müller, Sebastian Brunke, Sascha Molina, Juan Camilo Hube, Bernhard Schöck, Ulrike Guthke, Reinhard Kuchler, Karl Front Microbiol Microbiology The ability to adapt to diverse micro-environmental challenges encountered within a host is of pivotal importance to the opportunistic fungal pathogen Candida albicans. We have quantified C. albicans and M. musculus gene expression dynamics during phagocytosis by dendritic cells in a genome-wide, time-resolved analysis using simultaneous RNA-seq. A robust network inference map was generated from this dataset using NetGenerator, predicting novel interactions between the host and the pathogen. We experimentally verified predicted interdependent sub-networks comprising Hap3 in C. albicans, and Ptx3 and Mta2 in M. musculus. Remarkably, binding of recombinant Ptx3 to the C. albicans cell wall was found to regulate the expression of fungal Hap3 target genes as predicted by the network inference model. Pre-incubation of C. albicans with recombinant Ptx3 significantly altered the expression of Mta2 target cytokines such as IL-2 and IL-4 in a Hap3-dependent manner, further suggesting a role for Mta2 in host–pathogen interplay as predicted in the network inference model. We propose an integrated model for the functionality of these sub-networks during fungal invasion of immune cells, according to which binding of Ptx3 to the C. albicans cell wall induces remodeling via fungal Hap3 target genes, thereby altering the immune response to the pathogen. We show the applicability of network inference to predict interactions between host–pathogen pairs, demonstrating the usefulness of this systems biology approach to decipher mechanisms of microbial pathogenesis. Frontiers Research Foundation 2012-03-12 /pmc/articles/PMC3299011/ /pubmed/22416242 http://dx.doi.org/10.3389/fmicb.2012.00085 Text en Copyright © 2012 Tierney, Linde, Müller, Brunke, Molina, Hube, Schöck, Guthke and Kuchler. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited. |
spellingShingle | Microbiology Tierney, Lanay Linde, Jörg Müller, Sebastian Brunke, Sascha Molina, Juan Camilo Hube, Bernhard Schöck, Ulrike Guthke, Reinhard Kuchler, Karl An Interspecies Regulatory Network Inferred from Simultaneous RNA-seq of Candida albicans Invading Innate Immune Cells |
title | An Interspecies Regulatory Network Inferred from Simultaneous RNA-seq of Candida albicans Invading Innate Immune Cells |
title_full | An Interspecies Regulatory Network Inferred from Simultaneous RNA-seq of Candida albicans Invading Innate Immune Cells |
title_fullStr | An Interspecies Regulatory Network Inferred from Simultaneous RNA-seq of Candida albicans Invading Innate Immune Cells |
title_full_unstemmed | An Interspecies Regulatory Network Inferred from Simultaneous RNA-seq of Candida albicans Invading Innate Immune Cells |
title_short | An Interspecies Regulatory Network Inferred from Simultaneous RNA-seq of Candida albicans Invading Innate Immune Cells |
title_sort | interspecies regulatory network inferred from simultaneous rna-seq of candida albicans invading innate immune cells |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299011/ https://www.ncbi.nlm.nih.gov/pubmed/22416242 http://dx.doi.org/10.3389/fmicb.2012.00085 |
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